Background: Breast milk alone may not provide preterm infants with sufficient quantities of nutrients to support optimal growth and development. Mutli-nutrient fortifiers (powder or liquid supplements of protein, energy from carbohydrates or fat and other nutrients, usually extracted from cow's milk) can be added to breast milk to increase nutrient content by about 10%. Feeding preterm infants, particularly very preterm infants, with multi-nutrient fortified breast milk may increase nutrient intake and growth rates, and may improve development.

Study characteristics: We found 14 trials; most were small (involving 1071 infants in total) and were flawed methodologically.

Key results: Multi-nutrient fortification of breast milk for preterm infants is associated with small increases in rates of weight gain, length gain and head growth during neonatal unit admission. Only very limited data are available for growth and developmental outcomes assessed beyond infancy, and these show no effects of fortification. Trials report no consistent evidence of other potential benefits or harms of fortification, including effects on risk of feeding or bowel problems.

Conclusions: Although available trialdata show that multi-nutrient fortification increases growth rates of preterm infants during their initial hospital admission, they do not provide consistent evidence on effects on longer-term growth or development. Additional trials are needed to resolve this issue.

We used the standard search strategy of the Cochrane Neonatal Review Group. This included electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 2), MEDLINE, EMBASE and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (until February 2016), as well as conference proceedings and previous reviews.

We extracted data using the standard methods of the Cochrane Neonatal Review Group. We separately evaluated trial quality, data extracted by two review authors and data synthesised using risk ratios (RRs), risk differences and mean differences (MDs). We assessed the quality of evidence at the outcome level using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Main results:

We identified 14 trials in which a total of 1071 infants participated. The trials were generally small and weak methodologically. Meta-analyses provided low-quality evidence that multi-nutrient fortification of breast milk increases in-hospital rates of growth (MD 1.81 g/kg/d, 95% confidence interval (CI) 1.23 to 2.40); length (MD 0.12 cm/wk, 95% CI 0.07 to 0.17); and head circumference (MD 0.08 cm/wk, 95% CI 0.04 to 0.12). Only very limited data are available for growth and developmental outcomes assessed beyond infancy, and these show no effects of fortification. The data did not indicate other potential benefits or harms and provided low-quality evidence that fortification does not increase the risk of necrotising enterocolitis in preterm infants (typical RR 1.57, 95% CI 0.76 to 3.23; 11 studies, 882 infants).